tbuckley/cabot-search huggingface dataset:
Timing of Introduction of Complementary Foods — United States, 2016–2018
Authors: Katelyn V. Chiang, Heather C. Hamner, Ruowei Li, Cria G. Perrine
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

The American Academy of Pediatrics (AAP) recommends introducing complementary foods (i.e., any solid or liquid other than breast milk or infant formula) to infants at approximately age 6 months (1). Although a consensus on ideal timing is lacking, most experts agree that introduction of complementary foods before age 4 months is too early because of infant gastrointestinal and motor immaturity (1,2). In addition, early introduction prevents exclusively breastfed infants from reaching the recommended 6 months of exclusive breastfeeding (1) and might be associated with increased risk for overweight and obesity (3). Nationally representative data on complementary feeding are limited; state-level estimates have been previously unavailable. CDC analyzed 2016-2018 data from the National Survey of Children's Health (NSCH) (N = 23,743) to describe timing of complementary feeding introduction and prevalence of early introduction of complementary foods before age 4 months (early introduction) among children aged 1-5 years. Prevalence of early introduction was 15.6% nationally and varied geographically and across sociodemographic and infant feeding characteristics. These estimates suggest that approximately one in six infants are introduced to complementary foods before they are developmentally ready. Efforts by health care providers and others who might influence infant feeding practices could help decrease the number of infants who are introduced to complementary foods too early.
Genetic modification of inflammation- and clonal hematopoiesis–associated cardiovascular risk
Authors: Zhi Yu, Trevor P. Fidler, Yunfeng Ruan, Caitlyn Vlasschaert, Tetsushi Nakao, Md Mesbah Uddin, Taralynn Mack, Abhishek Niroula, J. Brett Heimlich, Seyedeh M. Zekavat, Christopher J. Gibson, Gabriel K. Griffin, Yuxuan Wang, Gina M. Peloso, Nancy Heard-Costa, Daniel Levy, Ramachandran S. Vasan, François Aguet, Kristin G. Ardlie, Kent D. Taylor, Stephen S. Rich, Jerome I. Rotter, Peter Libby, Siddhartha Jaiswal, Benjamin L. Ebert, Alexander G. Bick, Alan R. Tall, Pradeep Natarajan
Journal: Journal of Clinical Investigation (2023)

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with an increased risk of cardiovascular diseases (CVD), putatively via inflammasome activation. We pursued an inflammatory gene modifier scan for CHIP-associated CVD risk among 424,651 UK Biobank participants. CHIP was identified using whole exome sequencing data of blood DNA and modeled both as a composite and for common drivers (DNMT3A, TET2, ASXL1, and JAK2) separately. We developed predicted gene expression scores for 26 inflammasome-related genes and assessed how they modify CHIP-associated CVD risk. We identify IL1RAP as a potential key molecule for CHIP-associated CVD risk across genes and increased AIM2 gene expression leading to heightened JAK2- and ASXL1-associated CVD risks. We show that CRISPR-induced Asxl1 mutated murine macrophages have a particularly heightened inflammatory response to AIM2 agonism, associated with an increased DNA damage response, as well as increased IL-10 secretion, mirroring a CVD protective effect of IL10 expression in ASXL1 CHIP. Our study supports the role of inflammasomes in CHIP-associated CVD and provides new evidence to support gene-specific strategies to address CHIP-associated CVD risk.
Emerging Strategies in 3D Culture Models for Hematological Cancers
Authors: Dafne Barozzi, Cristina Scielzo
Journal: HemaSphere (2023)

In vitro cell cultures are fundamental and necessary tools in cancer research and personalized drug discovery. Currently, most cells are cultured using two-dimensional (2D) methods, and drug testing is mainly performed in animal models. However, new and improved methods that implement three-dimensional (3D) cell-culturing techniques provide compelling evidence that more advanced experiments can be performed, yielding valuable new insights. In 3D cell-culture experiments, the cell environment can be manipulated to mimic the complexity and dynamicity of the human tissue microenvironment, possibly leading to more accurate representations of cell-to-cell interactions, tumor biology, and predictions of drug response. The 3D cell cultures can also potentially provide alternative ways to study hematological cancers and are expected to eventually bridge the gap between 2D cell culture and animal models. The present review provides an overview of the complexity of the lymphoid microenvironment and a summary of the currently used 3D models that aim at recreating it for hematological cancer research. We here dissect the differences and challenges between, and potential advantages of, different culture methods and present our vision of the most promising future strategies in the hematological field.
Demographic Disparities in Mpox Vaccination Series Completion, by Route of Vaccine Administration — California, August 9, 2022–March 31, 2023
Authors: Tarek Salih, Josh Vance, Joshua Quint, Brenda Meza, Louise McNitt, Webster U. Lincoln, Robert Schechter
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

In August 2022, the Food and Drug Administration authorized JYNNEOS vaccine (modified vaccinia Ankara vaccine, Bavarian Nordic), a 2-dose series used for the prevention of Monkeypox virus infection, to be administered via a dose-sparing intradermal route, in addition to the previously authorized subcutaneous route.The California Department of Public Health investigated whether demographic disparities in vaccination series completion varied by route of administration of the recipient's first dose.Among California residents who received their first dose during August 9, 2022-March 31, 2023, a total of 59.8% received a second dose.Series completion was highest among non-Hispanic White persons (64.1%), persons aged ≥65 years (72.6%), and adults with male sex assignment at birth (62.1%); series completion was lowest among non-Hispanic Black or African American persons (51.3%), persons aged 18-24 years (42.9%), and adults assigned female sex at birth (42.8%).When the first dose was received by subcutaneous administration, overall series completion was 58.8% compared with 60.2% when the first dose was administered intradermally.Odds of series completion across all race and ethnicity groups, persons aged 18-64 years, community health conditions, and persons assigned male sex at birth were not greater when the first dose was administered subcutaneously compared with intradermally.Intradermal use of JYNNEOS vaccine did not lower overall 2-dose series completion rates.Continued efforts are needed to ensure persons at risk for Monkeypox virus infection receive both recommended doses.
Multi-omic rejuvenation and lifespan extension on exposure to youthful circulation
Authors: Bohan Zhang, David E. Lee, Alexandre Trapp, Alexander Tyshkovskiy, Ake T. Lu, Akshay Bareja, Csaba Kerepesi, Lauren K. McKay, Anastasia V. Shindyapina, Sergey E. Dmitriev, Gurpreet S. Baht, Steve Horvath, Vadim N. Gladyshev, James P. White
Journal: Nature Aging (2023)
<i>Notes from the Field:</i> Cruise Ship Norovirus Outbreak Associated with Person-to-Person Transmission — United States Jurisdiction, January 2023
Authors: Carolyn A. Crisp, Keisha A. Jenkins, Ian Dunn, Andrew Kupper, Jona Johnson, Stefanie White, Erin D. Moritz, Luis O. Rodriguez
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

CDC's Vessel Sanitation Program (VSP) monitors cases of acute gastroenteritis (AGE) on board cruise ships traveling to a U.S. port (1).Persons who have ≥3 loose stools (or more than normal for that person) within a 24-hour period or vomiting plus one other sign or symptom (e.g., fever, diarrhea, bloody stool, myalgia, abdominal cramps, or headache) meet the case definition for reportable AGE (2).When the percentage of passengers or crew members with AGE is ≥2% and the ship is due to arrive at a U.S. port within 15 days, the Maritime Illness Disease Reporting System alerts VSP and activates an investigation (1).During the first week of January 2023, VSP was notified of cases of AGE affecting >2% of passengers on board a ship that had completed three voyages in Europe and was within 15 days of arriving at a U.S. port (voyage 4)* (Figure).Ship medical crew members submitted stool samples from ill travelers for testing.All samples tested positive for norovirus genotype II.While the ship was sailing to a U.S. port, VSP monitored AGE cases on board and reviewed case data.By mid-January, passenger AGE prevalence reached 3.4%.
Pedunculopontine Chx10+ neurons control global motor arrest in mice
Authors: Haizea Goñi-Erro, Raghavendra Selvan, Vittorio Caggiano, Roberto Leiras, Ole Kiehn
Journal: Nature Neuroscience (2023)

Abstract Arrest of ongoing movements is an integral part of executing motor programs. Behavioral arrest may happen upon termination of a variety of goal-directed movements or as a global motor arrest either in the context of fear or in response to salient environmental cues. The neuronal circuits that bridge with the executive motor circuits to implement a global motor arrest are poorly understood. We report the discovery that the activation of glutamatergic Chx10-derived neurons in the pedunculopontine nucleus (PPN) in mice arrests all ongoing movements while simultaneously causing apnea and bradycardia. This global motor arrest has a pause-and-play pattern with an instantaneous interruption of movement followed by a short-latency continuation from where it was paused. Mice naturally perform arrest bouts with the same combination of motor and autonomic features. The Chx10-PPN-evoked arrest is different to ventrolateral periaqueductal gray-induced freezing. Our study defines a motor command that induces a global motor arrest, which may be recruited in response to salient environmental cues to allow for a preparatory or arousal state, and identifies a locomotor-opposing role for rostrally biased glutamatergic neurons in the PPN.
COVID-19 is linked to changes in the time–space dimension of human mobility
Authors: Clodomir Santana, Federico Botta, Hugo Barbosa, Filippo Privitera, Ronaldo Menezes, Riccardo Di Clemente
Journal: Nature Human Behaviour (2023)

Socio-economic constructs and urban topology are crucial drivers of human mobility patterns. During the coronavirus disease 2019 pandemic, these patterns were reshaped in their components: the spatial dimension represented by the daily travelled distance, and the temporal dimension expressed as the synchronization time of commuting routines. Here, leveraging location-based data from de-identified mobile phone users, we observed that, during lockdowns restrictions, the decrease of spatial mobility is interwoven with the emergence of asynchronous mobility dynamics. The lifting of restriction in urban mobility allowed a faster recovery of the spatial dimension compared with the temporal one. Moreover, the recovery in mobility was different depending on urbanization levels and economic stratification. In rural and low-income areas, the spatial mobility dimension suffered a more considerable disruption when compared with urbanized and high-income areas. In contrast, the temporal dimension was more affected in urbanized and high-income areas than in rural and low-income areas.
Targeting collagen XVIII improves the efficiency of ErbB inhibitors in breast cancer models
Authors: Raman Devarajan, Valerio Izzi, Hellevi Peltoketo, Gunilla Rask, Saila Kauppila, Marja-Riitta Väisänen, Heli Ruotsalainen, Guillermo Martínez-Nieto, Sanna-Maria Karppinen, Timo Väisänen, Inderjeet Kaur, Jussi Koivunen, Takako Sasaki, Robert Winqvist, Aki Manninen, Fredrik Wärnberg, Malin Sund, Taina Pihlajaniemi, Ritva Heljasvaara
Journal: Journal of Clinical Investigation (2023)

The tumor extracellular matrix (ECM) critically regulates cancer progression and treatment response. Expression of the basement membrane component collagen XVIII (ColXVIII) is induced in solid tumors, but its involvement in tumorigenesis has remained elusive. We show here that ColXVIII was markedly upregulated in human breast cancer (BC) and was closely associated with a poor prognosis in high-grade BCs. We discovered a role for ColXVIII as a modulator of epidermal growth factor receptor tyrosine kinase (ErbB) signaling and show that it forms a complex with ErbB1 and -2 (also known as EGFR and human epidermal growth factor receptor 2 [HER2]) and α6-integrin to promote cancer cell proliferation in a pathway involving its N-terminal portion and the MAPK/ERK1/2 and PI3K/AKT cascades. Studies using Col18a1 mouse models crossed with the mouse mammary tumor virus-polyoma virus middle T antigen (MMTV-PyMT) mammary carcinogenesis model showed that ColXVIII promoted BC growth and metastasis in a tumor cell-autonomous manner. Moreover, the number of mammary cancer stem cells was significantly reduced in the MMTV-PyMT and human cell models upon ColXVIII inhibition. Finally, ablation of ColXVIII substantially improved the efficacy of ErbB-targeting therapies in both preclinical models. In summary, ColXVIII was found to sustain the stemness properties of BC cells and tumor progression and metastasis through ErbB signaling, suggesting that targeting ColXVIII in the tumor milieu may have important therapeutic potential.
Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: phase 1/2 trial interim results
Authors: Raffit Hassan, Marcus Butler, Roisin E. O’Cearbhaill, David Y. Oh, Melissa Johnson, Kevin Zikaras, Munisha Smalley, Michael Ross, Janos L. Tanyi, Azam Ghafoor, Nirali N. Shah, Babak Saboury, Liang Cao, Alfonso Quintás-Cardama, David Hong
Journal: Nature Medicine (2023)

Abstract The T cell receptor fusion construct (TRuC) gavocabtagene autoleucel (gavo-cel) consists of single-domain anti-mesothelin antibody that integrates into the endogenous T cell receptor (TCR) and engages the signaling capacity of the entire TCR upon mesothelin binding. Here we describe phase 1 results from an ongoing phase1/2 trial of gavo-cel in patients with treatment-refractory mesothelin-expressing solid tumors. The primary objectives were to evaluate safety and determine the recommended phase 2 dose (RP2D). Secondary objectives included efficacy. Thirty-two patients received gavo-cel at increasing doses either as a single agent ( n = 3) or after lymphodepletion (LD, n = 29). Dose-limiting toxicities of grade 3 pneumonitis and grade 5 bronchioalveolar hemorrhage were noted. The RP2D was determined as 1 × 10 8 cells per m 2 after LD. Grade 3 or higher pneumonitis was seen in 16% of all patients and in none at the RP2D; grade 3 or higher cytokine release syndrome occurred in 25% of all patients and in 15% at the RP2D. In 30 evaluable patients, the overall response rate and disease control rate were 20% (13% confirmed) and 77%, respectively, and the 6-month overall survival rate was 70%. Gavo-cel warrants further study in patients with mesothelin-expressing cancers given its encouraging anti-tumor activity, but it may have a narrow therapeutic window. ClinicalTrials.gov identifier: NCT03907852 .
The MLL–Menin Interaction is a Therapeutic Vulnerability in NUP98-rearranged AML
Authors: Milad Rasouli, Helen Blair, Selina Troester, Katarzyna Szoltysek, Rachel Cameron, Minoo Ashtiani, Anja Krippner-Heidenreich, Florian Grebien, Gerard McGeehan, C. Michel Zwaan, Olaf Heidenreich
Journal: HemaSphere (2023)

Chromosomal translocations involving the
A reinforcement learning model for AI-based decision support in skin cancer
Authors: Catarina Barata, Veronica Rotemberg, Noel C. F. Codella, Philipp Tschandl, Christoph Rinner, Bengu Nisa Akay, Zoe Apalla, Giuseppe Argenziano, Allan Halpern, Aimilios Lallas, Caterina Longo, Josep Malvehy, Susana Puig, Cliff Rosendahl, H. Peter Soyer, Iris Zalaudek, Harald Kittler
Journal: Nature Medicine (2023)

We investigated whether human preferences hold the potential to improve diagnostic artificial intelligence (AI)-based decision support using skin cancer diagnosis as a use case. We utilized nonuniform rewards and penalties based on expert-generated tables, balancing the benefits and harms of various diagnostic errors, which were applied using reinforcement learning. Compared with supervised learning, the reinforcement learning model improved the sensitivity for melanoma from 61.4% to 79.5% (95% confidence interval (CI): 73.5-85.6%) and for basal cell carcinoma from 79.4% to 87.1% (95% CI: 80.3-93.9%). AI overconfidence was also reduced while simultaneously maintaining accuracy. Reinforcement learning increased the rate of correct diagnoses made by dermatologists by 12.0% (95% CI: 8.8-15.1%) and improved the rate of optimal management decisions from 57.4% to 65.3% (95% CI: 61.7-68.9%). We further demonstrated that the reward-adjusted reinforcement learning model and a threshold-based model outperformed naïve supervised learning in various clinical scenarios. Our findings suggest the potential for incorporating human preferences into image-based diagnostic algorithms.
Geographic Distribution of Suspected Alpha-gal Syndrome Cases — United States, January 2017–December 2022
Authors: Julie M. Thompson, Ann Carpenter, Gilbert J. Kersh, Tyler Wachs, Scott P. Commins, Johanna S. Salzer
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Alpha-gal syndrome (AGS) is an emerging, tick bite-associated allergic condition characterized by a potentially life-threatening immunoglobulin E (IgE)-mediated hypersensitivity to galactose-alpha-1,3-galactose (alpha-gal), an oligosaccharide found in most nonprimate mammalian meat and products derived from these mammals. Specific symptoms and severity of AGS vary among persons, and no treatment or cure is currently available. During 2010-2018, more than 34,000 suspected cases of AGS were identified in the United States, but current knowledge of where cases occur is limited. This study examined alpha-gal-specific IgE (sIgE) antibody testing results submitted to the commercial laboratory responsible for nearly all testing in the United States before 2022 to assess the geographic distribution and magnitude of this emerging condition. During January 1, 2017-December 31, 2022, a total of 357,119 tests were submitted from residences in the United States, corresponding to 295,400 persons. Overall, 90,018 (30.5%) persons received a positive test result in the study period, and the number of persons with positive test results increased from 13,371 in 2017 to 18,885 in 2021. Among 233,521 persons for whom geographic data were available, suspected cases predominantly occurred in counties within the southern, midwestern, and mid-Atlantic U.S. Census Bureau regions. These data highlight the evolving emergence of AGS and can be used to help state and local health agencies initiate surveillance and target public health outreach and health care provider education to high-risk localities.
Alarming decline in vaccine uptake must be tackled, say MPs
Authors: Matt Limb
Journal: BMJ (2023)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Alarming decline in vaccine uptake must be tackled, say MPs Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Detection of low-frequency mutations in clinical samples by increasing mutation abundance via the excision of wild-type sequences
Authors: Wei Chen, Haiqi Xu, Shenbin Dai, Jiayu Wang, Ziyu Yang, Yuewen Jin, Mengbing Zou, Xianjin Xiao, Tongbo Wu, Wei Yan, Bin Zhang, Zhimiao Lin, Meiping Zhao
Journal: Nature Biomedical Engineering (2023)
Evoking natural thermal perceptions using a thin-film thermoelectric device with high cooling power density and speed
Authors: Luke E. Osborn, Rama Venkatasubramanian, Meiyong Himmtann, Courtney W. Moran, Jonathan M. Pierce, Priya Gajendiran, Jared M. Wormley, Richard J. Ung, Harrison H. Nguyen, Adam C. G. Crego, Matthew S. Fifer, Robert S. Armiger
Journal: Nature Biomedical Engineering (2023)
Short-term effects of a speech feminization program for transgender women: listener perceptions, self-perception and satisfaction of the voice
Authors: Clara Leyns, Iris Meerschman, Guy T’Sjoen, Evelien D’haeseleer
Journal: International Journal of Transgender Health (2023)

This study measured and compared the short-term impact of pitch elevation training (PET) and articulation-resonance training (ART) in transgender women, on self-perception, satisfaction and masculinity-femininity perceptions of listeners.
Six-week oral prednisolone therapy for immune-related pneumonitis: a single-arm phase II study
Authors: Masato Karayama, Naoki Inui, Yusuke Inoue, Hideki Yasui, Hironao Hozumi, Yuzo Suzuki, Kazuki Furuhashi, Tomoyuki Fujisawa, Noriyuki Enomoto, Kazuhiro Asada, Tomohiro Uto, Masato Fujii, Takashi Matsui, Shun Matsuura, Dai Hashimoto, Mikio Toyoshima, Masaki Ikeda, Hiroyuki Matsuda, Nao Inami, Yusuke Kaida, Satoshi Funayama, Shintaro Ichikawa, Satoshi Goshima, Takafumi Suda
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background There has been no prospective trial for treatment of immune-related pneumonitis (irP) occurred after immune checkpoint inhibitors (ICIs). Methods In this single-arm phase II study, patients with cancer with grade ≥2 irP received oral prednisolone (1 mg/kg/day), tapered over 6 weeks. The primary endpoint was a pneumonitis control rate at 6 weeks from the start of the study treatment, defined as complete disappearance or partial improvement of irP in high-resolution CT of the chest. Results Among 57 patients enrolled, 56 were included in the final analysis. The most frequent cause of irP was single ICI therapy (51.8%), followed by combination with chemotherapy plus ICI (39.3%). Thirty-five (62.5%) patients had grade 2 irP and 21 (37.5%) had grade ≥3. Fifty-one (91.1%) patients completed the study treatment while 5 discontinued the study treatment because of relapse of irP (n=1), death from cancer (n=1), occurrence of immune-related hepatitis (n=1), extension of the treatment duration more than 6 weeks (n=1), and attending physician’s decision (n=1). Six weeks after the start of the study treatment, 16 (28.5%) patients demonstrated complete recovery from irP, 35 (62.5%) had a partial improvement in irP, 1 (1.8%) had a relapse of irP, and 4 (7.1%) were not evaluable. The pneumonitis control rate at 6 weeks was 91.1% (95% CI, 80.7% to 96.1%). Twelve weeks after the start of the study treatment, 5 (8.9%), 27 (48.2%), and 15 (26.8%) patients demonstrated complete recovery, partial improvement, and relapse, respectively, and 9 (16.1%) were not evaluable. The pneumonitis control rate at 12 weeks was 57.1% (95% CI, 44.1% to 69.2%). During the observation period, 18 (32.1%) patients experienced a relapse of irP, and of those, 17 received re-treatment with corticosteroids. Grade ≥3 adverse events occurred in 10 (17.9%) patients, in which hyperglycemia was most frequent (n=6). There was no treatment-related death. Conclusions In this first prospective study for irP, prednisolone at 1 mg/kg/day, tapered over 6 weeks, demonstrated a promising clinical benefit and manageable toxicity, suggesting a potential treatment option for irP. Trial registration number jRCT: 1041190029.